Journal Article

Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor

Agnoletto, Andrea, Sflomos, George, Brisken, Cathrin, Battista, Laura, Ambrosini, Giovanna, Treboux, Assia, Scabia, Valentina, De Martino, Fabio, Zaman, Khalil, Ayyanan, Ayyakkannu, Stravodimou, Athina, Bucher, Philip, Fiche, Maryse, Laszlo, Csaba, Jallut, Didier

2022

Overview

Estrogen and progesterone receptor (ER, PR) signaling control breast development and impinge on breast carcinogenesis. ER is an established driver of ER + disease but the role of the PR, itself an ER target gene, is debated. We assess the issue in clinically relevant settings by a genetic approach and inject ER + breast cancer cell lines and patient-derived tumor cells to the milk ducts of immunocompromised mice. Such ER + xenografts were exposed to physiologically relevant levels of 17-β-estradiol (E2) and progesterone (P4). We find that independently both premenopausal E2 and P4 levels increase tumor growth and combined treatment enhances metastatic spread. The proliferative responses are patient-specific with MYC and androgen receptor (AR) signatures determining P4 response. PR is required for tumor growth in patient samples and sufficient to drive tumor growth and metastasis in ER signaling ablated tumor cells. Our findings suggest that endocrine therapy may need to be personalized, and that abrogating PR expression can be a therapeutic option. The role of progesterone receptor (PR) and its interplay with estrogen receptor (ER) in breast cancer is controversial. Here, the authors demonstrate that PR can have an ER-independent role in breast cancer growth and metastasis and that its effects are dependent on MYC and androgen receptor signatures.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 17β-Estradiol / 38 / 38/1 / 45 / 45/91 / 59 / 59/5 / 631/67/1347 / 64 / 64/60 / 692/420/755 / 82/51 / Ablation / Androgen receptors / Androgens / Animals / Breast cancer / Breast Neoplasms - metabolism / Carcinogenesis / Carcinogens / Combined treatment / Endocrine therapy / Estradiol - pharmacology / Estradiol - therapeutic use / Estrogen receptors / Estrogens / Female / Humanities and Social Sciences / Humans / Metastases / Metastasis / Mice / multidisciplinary / Myc protein / Patients / Progesterone / Progesterone - pharmacology / Receptors / Receptors, Estrogen - genetics / Receptors, Estrogen - metabolism / Receptors, Progesterone - genetics / Receptors, Progesterone - metabolism / Science / Science (multidisciplinary) / Sex hormones / Signaling / Signatures / Tumor cell lines / Tumor cells / Tumors / Xenografts / Xenotransplantation